It is highly desirable to attenuate aging and extend human lifespan, but the complex etiology of aging leaves potential drug targets unclear. While treatments exist for some symptoms of age related disorders, no treatments are available that address all aspect of aging simultaneously. There is, therefore a need for new treatment to extend lifespan and treat, or delay the onset of, age-related conditions and disorders.
Xenobiotic metabolism is a complex, highly regulated and energetically costly process whose major function is biotransformation and elimination from the body of lipophilic toxic molecules that are generated as products of metabolism (endobiotics) or absorbed from the environment (xenobiotics). This process involves a large battery of enzymes, mainly expressed in the liver and the gastrointestinal tract and transcriptionally regulated by several nuclear receptors (NRs). Phase I xenobiotic metabolism enzymes, such as cytochrome P450s, catalyze biotransformation reactions (e.g. hydroxylation) to functionalize the chemically inert xenobiotic molecules for further modifications that occur during Phase II. Phase II enzymes (including UDP-glucuronosyltransferases and glutathione transferases) catalyze covalent attachment of polar side groups to functionalized xenobiotic molecules, increasing their solubility and promoting their excretion.
Slowing down aging is predicted to yield greater benefits for human health than curing cancer and heart disease combined (Goldman 2013). Despite significant progress in recent years, the underlying biochemical pathways that determine longevity are not fully understood.